Immunohistochemical analyses of neural stem cell lineage markers in normal feline brains and glial tumors.

Neural stem cell (NSC) lineage cells have not been fully identified in feline brains, and the NSC-like nature of feline glial tumors has not been determined. In this study, 6 normal cat brains (3 newborn and 3 older cats) and 13 feline glial tumors were analyzed using immunohistochemical NSC lineage markers. The feline glial tumors were subjected to immunohistochemical scoring followed by hierarchical cluster analysis. In newborn brains, glial acidic fibrillary protein (GFAP)/nestin/sex-determining region Y-box transcription factor 2 (SOX2)-immunopositive NSCs, SOX2-immunopositive intermediate progenitor cells, oligodendrocyte transcription factor 2 (OLIG2)/platelet-derived growth factor receptor-α (PDGFR-α)-immunopositive oligodendrocyte precursor cells (OPCs), OLIG2/GFAP-immunopositive immature astrocytes, and neuronal nuclear (NeuN)/ß-3 tubulin-immunopositive mature neuronal cells were observed. The apical membrane of NSCs was also immunopositive for Na+/H+ exchanger regulatory factor 1 (NHERF1). In mature brains, the NSC lineage cells were similar to those of the newborn brains. A total of 13 glial tumors consisted of 2 oligodendrogliomas, 4 astrocytomas, 3 subependymomas, and 4 ependymomas. Astrocytomas, subependymomas, and ependymomas were immunopositive for GFAP, nestin, and SOX2. Subependymomas and ependymomas showed dot-like or apical membrane immunolabeling for NHERF1, respectively. Astrocytomas were immunopositive for OLIG2. Oligodendrogliomas and subependymomas were immunopositive for OLIG2 and PDGFR-α. Feline glial tumors also showed variable immunolabeling for ß-3 tubulin, NeuN, and synaptophysin. Based on these results, feline astrocytomas, subependymomas, and ependymomas appear to have an NSC-like immunophenotype. In addition, astrocytomas, subependymomas, and ependymomas have the characteristics of glial, oligodendrocyte precursor, and ependymal cells, respectively. Feline oligodendrogliomas likely have an OPC-like immunophenotype. In addition, feline glial tumors may have multipotential stemness for differentiation into neuronal cells. These preliminary results should be validated by gene expression analyses in future studies with larger case numbers.

A review of primary central nervous system neoplasms of cats.

Primary central nervous system (CNS) neoplasms are uncommonly diagnosed in cats. The majority of primary feline CNS neoplasms described in the veterinary literature consist of meningioma and glioma occurring mainly in the brain and less often in the spinal cord. Although most neoplasms can be diagnosed based on routine histologic evaluation, less typical tumors need to be further characterized using immunohistochemistry. This review compiles the relevant information about the most common primary CNS neoplasms of cats available in the veterinary literature, aiming to serve as a converging source of information for the topic.

OLIG2 immunolabeling in feline ependymoma.

Ependymoma, one of the most common gliomas in cats, occurs most often in the lateral and third ventricles and has variable histologic patterns that often form rosettes and pseudorosettes. Oligodendrocyte transcription factor (OLIG2) is expressed in oligodendrocyte precursor cells and mature oligodendrocytes. Although widely used as a diagnostic marker for most gliomas, OLIG2 is reported to have minimal immunolabeling in ependymomas. Here we characterize the OLIG2 immunolabeling pattern in 19 cases of feline ependymoma, which occurred predominantly in the lateral and third ventricles. Immunohistochemistry for GFAP was variable in 14 cases and was typically localized in the cytoplasmic processes of the neoplastic ependymal cells, especially in the rosettes and pseudorosettes. Nuclear OLIG2 immunolabeling was present in 17 cases and varied in intensity from weak (4 cases) to strong (13 cases). The distribution of OLIG2 immunolabeling within the neoplasms included none (2 cases), <25% (7 cases), 25-50% (6 cases), 51-75% (2 cases), and >75% (3 cases). OLIG2 immunolabeling intensity and distribution is widespread in feline ependymoma, in contrast to ependymomas in other species, and should not be relied upon as a specific marker for feline oligodendroglioma.

Magnetic resonance imaging findings and antemortem cytologic diagnosis of intramedullary spinal cord ependymoma in a dog.

CASE DESCRIPTION: A 3-year-old 31.1-kg castrated male mixed-breed dog was evaluated because of a 1- to 2-week history of paraparesis, knuckling of the hind feet, and difficulty posturing to urinate or defecate. CLINICAL FINDINGS: The dog was paraparetic but weakly ambulatory with a kyphotic posture, a mildly decreased patellar reflex in the right pelvic limb, increased tone in both pelvic limbs, and marked hyperesthesia on paraspinal palpation of the lumbar region. The urinary bladder was enlarged and firm on palpation. Neuroanatomic findings were primarily consistent with localization to the T3-L3 spinal cord segments. Magenetic resonance imaging of the thoracolumbar spinal column revealed a discrete intramedullary spinal cord mass from the cranial aspect of L4 to the middle of L5. The mass was sampled by fine-needle aspiration, and on cytologic evaluation, the suspected diagnosis was an ependymoma. TREATMENT AND OUTCOME: Owing to poor prognosis and limited treatment options, the owner elected euthanasia. Postmortem examination of the spinal cord and histologic findings for samples of the mass supported a likely diagnosis of ependymoma. CLINICAL RELEVANCE: Ependymoma is a rare neoplasm in dogs but should be considered in young patients with evidence of a tumor in the CNS. Fine-needle aspiration of the spinal cord mass was possible in the dog of this report, and the cytologic findings provided useful diagnostic information.

Brain Ependymoma in an African Grey Parrot (Psittacus erithacus erithacus).

A 14-year-old unsexed African grey parrot (Psittacus erithacus erithacus) was presented with a 12-hour history of neurological signs and vomiting. The external physical examination of the patient revealed lethargy, moderate hypothermia, a head tilt, and horizontal nystagmus. Whole-body radiographic imaging and blood biochemistry parameters were unremarkable, and a serological test to detect bornavirus was negative. A computed tomography scan of the bird revealed a large cystic lesion located on the fourth ventricle of the brain. In spite of treatment (nonsteroidal anti-inflammatory drugs and antibiotic and antiparasitic therapy), the parrot's health continued to decline, and it was euthanatized 12 days after presentation. A complete postmortem examination was performed on the patient's brain. Histopathological interpretation of tissues submitted described a large neoformation composed of cells arranged in perivascular pseudorosettes. Hyperchromatic nuclei and marked anisokaryosis were suggestive of a malignant tumor. The tissue mass was associated with significant dilation of the fourth ventricle and a severe peripheral gliosis. The histopathological diagnosis of the neoformation was an ependymoma. Ependymomas are glial tumors of the ependymal cells that line the central canal and the ventricles of the brain and are rarely described in mammals. In birds, ependymomas were only described in budgerigars (Melopsittacus undulatus). In human medicine, the recommended treatment is surgical removal of the tumor when possible, followed by radiotherapy.

Ependymoma in a dwarf goat.

Ependymomas are relatively rare neuroglial tumours that derive from ependymal cells, lining the ventricles of the brain and the central canal of the spinal cord. They occur particularly in dogs, while reports in goats are extremely scarce. A 15-year-old female dwarf goat was found in lateral recumbency, developed opisthotonus and was killed humanely. Necropsy revealed a well-demarcated, non-encapsulated mass in the diencephalon at the level of the interthalamic adhesion. Histologically, the neoplasm showed highly cellular sheets of tumour cells with occasional perivascular pseudorosettes and true rosettes. Immunohistochemistry revealed an extensive and perivascularly accentuated expression of S100 protein and glial fibrillary acidic protein, while vimentin expression was observed to a minor extent. Tumour cells were negative for cytokeratin and CNPase. Ultrastructurally, intercellular junctions were present, but cilia and blepharoblasts were lacking. The presented findings are consistent with a cellular subtype of an ependymoma. Ependymomas should be regarded as a rare cause of central nervous signs in goats.

Canine Ependymoma: Diagnostic Criteria and Common Pitfalls.

Reports of canine ependymoma are generally restricted to single case reports with tumor incidence estimated at 2% to 3% of primary central nervous system (CNS) tumors. While most commonly reported in the lateral ventricle, tumors can occur anywhere in the ventricular system and in extraventricular locations. Rosettes and pseudorosettes are a common histologic feature; however, these features can be mimicked by other CNS neoplasms. Thirty-seven potential ependymoma cases were identified in a retrospective database search of 8 institutions, and a histologic review of all cases was conducted. Of 37 cases, 22 candidate cases were further subjected to a consensus histologic and immunohistochemical review, and only 5 of 37 (13.5%) were conclusively identified as ependymoma. The neuroanatomic locations were the lateral ventricle (3/5), third ventricle (1/5), and mesencephalic aqueduct (1/5). Subtypes were papillary (4/5) and tanycytic (1/5). Histologic features included rosettes (5/5), pseudorosettes (5/5), ependymal canals (2/5), tanycytic differentiation (1/5), blepharoplasts (1/5), ciliated cells (1/5), and high nuclear to cytoplasmic ratio (5/5). Immunolabeling for GFAP (4/4) and CKAE1/3 (3/4) was found in pseudorosettes, rosettes, and scattered individual neoplastic cells. Diffuse but variably intense cytoplasmic S100 immunolabeling was detected in 3 of 4 cases. Olig2 intranuclear immunolabeling was observed in less than 1% of the neoplastic cells (3/3). Tumors that had pseudorosettes and mimicked ependymoma included oligodendroglioma, choroid plexus tumor, pituitary corticotroph adenoma, papillary meningioma, and suprasellar germ cell tumor. These findings indicate that canine ependymoma is an extremely rare neoplasm with histomorphologic features that overlap with other primary CNS neoplasms.

MAGNETIC RESONANCE IMAGING FEATURES OF INTRAVENTRICULAR EPENDYMOMAS IN Five CATS.

Intraventricular ependymoma is a rare type of feline intracranial neoplasia and published information on magnetic resonance imaging (MRI) characteristics is currently lacking. The purpose of this retrospective case series study was to describe the clinical and MRI characteristics of histopathologically confirmed intraventricular ependymomas in a group of cats. Five cats met inclusion criteria. In relation to normal gray matter, ependymomas appeared hyperintense on T2W, T2W-FLAIR, PD, and DW-EPI images; isointense on ADC images; and had subtle to strong contrast enhancement. Some variability was seen on T2*GRE and on T1W images with masses being isointense to hyperintense. Four ependymomas were small and homogeneous, and one was centrally cavitated. All cats had obstructive hydrocephalus, transtentorial herniation, and foramen magnum herniation. Perilesional edema was identified in most cats but was questionable in one. Intraventricular ependymoma should be considered as a differential diagnosis for cats with this combination of MRI signs.

Spontaneous high-grade glial intramedullary tumor of the spine in a rhesus macaque (Macaca mulatta).

BACKGROUND: A 4-year-old rhesus macaque presented with acute, progressive paresis of the extremities. METHODS: A complete blood count, serum biochemical analysis, neurologic exam and necropsy were performed. RESULTS: The clinical, histopathological, and immunohistochemical findings confirmed a high-grade intramedullary glial tumor of the spinal cord that was most consistent with an ependymoma. CONCLUSIONS: We describe a case of a naturally occurring spontaneous spinal cord neoplasia in a non-human primate.

Clear cell ependymoma in a dog.

A 13-year-old, mixed breed dog presented with a 1-month history of seizures. Magnetic resonance imaging of the brain revealed a 2.2 × 1.0 × 0.9 cm ovoid and elongate cystic mass within the white matter of the left frontal lobe extending caudally from the cribriform plate to the rostral left lateral ventricle. Three fractions of stereotactic radiotherapy were administered and resulted in reduction of the volume of the tumour; however, the clinical signs failed to improve. On post-mortem examination, a single mass 1.5 × 0.3 × 1 cm was found within the left frontal lobe. It consisted of gelatinous, grey, friable tissue bordering a central empty cavity. Microscopical evaluation revealed polygonal neoplastic cells with distinct cytoplasmic borders and one or more intracytoplasmic solid, brightly eosinophilic, sharply defined globules. Immunohistochemically, the neoplastic cells expressed glial fibrillary acidic protein and S100 but were negative for pan cytokeratin, vimentin, olig-2 and synaptophysin. Ultrastructurally, neoplastic cells had dense whorls of intracytoplasmic intermediate filaments and were connected by multiple intermittent long zonula adherens-type junctions. Based on these findings, a diagnosis of clear cell ependymoma was made. This is the first report of this subtype in the dog.

Ventricular and extraventricular ependymal tumors in 18 cats.

Ependymal tumors are reported rarely in domestic animals. The aims of this study were to examine the clinical and pathologic features of ventricular and extraventricular ependymomas and subependymomas in 18 domestic cats examined between 1978 and 2011. Parameters examined included age, sex, breed, clinical signs, and macroscopic and histopathologic features. The mean age of affected cats was 9 years, 4 months; median age, 8.5 years. There were 8 female and 4 male cats, and 6 cats for which sex was not recorded. Breeds included 10 domestic shorthaired, 2 domestic longhaired, 1 Persian, and 1 Siamese. Clinical signs included altered mentation or behavior, seizures, circling, propulsive gait, generalized discomfort, and loss of condition. The tumors often formed intraventricular masses and usually arose from the lining of the lateral or third ventricles, followed by the fourth ventricle, mesencephalic aqueduct, and spinal cord central canal. Three tumors were extraventricular, forming masses within the cerebrum and adjacent subarachnoid space. Histologically, 15 tumors were classified as variants of ependymomas (classic, papillary, tanycytic, or clear cell) and 3 as subependymomas. Tumors were generally well demarcated; however, 6 ependymomas focally or extensively infiltrated the adjacent neural parenchyma. Characteristic perivascular pseudorosettes were observed in all ependymomas; true rosettes were less common. Some tumors had areas of necrosis, mineralization, cholesterol clefts, and/or hemorrhage. This cohort study of feline ependymal tumors includes subependymoma and primary extraventricular ependymoma, variants not previously described in the veterinary literature but well recognized in humans.

Cachexia secondary to intracranial anaplastic (malignant) ependymoma in a boxer dog.

An eight-year-old female boxer was referred because of weight loss of several months' duration. On physical examination, cachexia was the only reported abnormality. Neurological symptoms were shown only in the last days preceding death and consisted of altered mental status, compulsive behaviour and left rear proprioception deficit. At post-mortem examination, a voluminous, soft, haemorrhagic mass was found invading the floor of the brain. Based on the morphological features of the tumour, marked parenchymal invasion, extensive necrosis and cellular atypia, the mass was classified as an anaplastic ependymoma. This case report shows similarities to the diencephalic syndrome reported in human paediatric medicine in which the main clinical sign is a profound emaciation in spite of normal or slightly diminished caloric intake. Weight loss and cachexia are clinically relevant problems in small animals and these clinical signs should raise a suspicion, among the other differentials, of a brain tumour, even in absence of neurologic signs.

Analysis of blood flow in a third ventricular ependymoma and an olfactory bulb meningioma by using perfusion computed tomography.

Brain perfusion computed tomography (CT) scanning was performed in a mongrel dog and a golden retriever that were diagnosed with third ventricular tumor and olfactory bulb tumor, respectively, by contrast-enhanced CT. The tumors were pathologically diagnosed as ependymoma and meningioma, respectively. Perfusion CT results revealed that the ependymoma in this study had a lower blood flow, higher blood volume, and greater transit time of blood than the adjacent brain tissue. Further, the meningioma in this study had a higher blood flow, higher blood volume, and greater transit time of blood than the adjacent brain tissue. Perfusion CT can potentially be used for the grading of brain tumors and narrowing differential diagnosis, provided the perfusion CT data of animals are accumulated.

Ventricular ependymoma in a German Shepherd dog.

Using magnetic resonance imaging (MRI) together with clinical, pathomorphological and immunohistological methods, a ependymoma is described in a 9-year-old German Shepherd dog, which presented with behavioural and oculocephalic responses and generalised ataxia. The ependymoma, 9 x 6 x 5mm in size, was localised intra-axially in the right interventricular foramen and hydrocephalus was observed by MRI. Microscopically, the tumour was composed of pseudorosettes, and immunohistochemical examination revealed vimentin and glial fibrillary acidic protein immunoreactivity in the neoplastic cells.

Surgical and radiotherapy treatment of a spinal cord ependymoma in a dog.

A 4-year-old Beagle dog was presented for investigation of a left pelvic limb gait abnormality. Neurolocalisation indicated a lumbar (L2 to L5) spinal cord lesion. On magnetic resonance imaging (MRI), an intramedullary mass was demonstrated at L3. The mass was partially removed under general anaesthesia and a diagnosis of ependymoma was made on histological examination. The dog was treated with postoperative orthovoltage x-ray radiation (total dose; 44 Gy given in 11 fractions over a 4 week period) combined with low dose carboplatin (25 mg/m2). The dog was alive 16 months after surgery without further neurological deficits. No further tumour growth was detected on subsequent MRI evaluations.

Microarray analysis of differentially expressed genes of primary tumors in the canine central nervous system.

The pathophysiologic similarities of many human and canine cancers support the role of the domestic dog as a model for brain tumor research. Here we report the construction of a custom canine brain-specific cDNA microarray and the analysis of gene expression patterns of several different types of canine brain tumor. The microarray contained 4000 clones from a canine brain specific cDNA library including 2161 clones that matched known genes or expressed sequence tags (ESTs) and 25 cancer-related genes. Our study included 16 brain tumors (seven meningiomas, five glial tumors, two ependymomas, and two choroid plexus papillomas) from a variety of different dog breeds. We identified several genes previously found to be differentially expressed in human brain tumors. This suggests that human and canine brain tumors share a common pathogenesis. In addition, we also found differentially expressed genes unique to either meningiomas or the glial tumors. This report represents the first global gene expression analysis of different types of canine brain tumors by cDNA microarrays and might aid in the identification of potential candidate genes involved in tumor formation and progression.

Anaplastic ependymoma in the cervical spinal cord of a maltese dog.

An 8-year and 6-month-old female Maltese dog showed a stoop with rigidity of her cervix and back. Neurologic examination showed loss of proprioception, and deficiency of pain response. Postmortem examination revealed the neoplastic mass replacing the central area in the cervical spinal cord at the level from 4th to 5th segments. Histologically, the mass was composed of neoplastic ependymal cells. The neoplastic cells showed marked atypism, and occasionally formed ependymal rosettes. Based on the morphologic features, the tumor was diagnosed as anaplastic ependymoma. Immunohistochemistry showed that the neoplastic cells were negative for glial fibrillary acid protein, and slightly positive for vimentin and cytokeratin.

First cases of animal diseases published since 2000. 5. Sheep.

In this fifth article of a series of papers listing first case reports of animal diseases published since 2000, the following five cases of sheep diseases are discussed: Ependymoma. Mastitis caused by Burkholderia cepacia infection. Meningoencephalitis associated with Globicatella sanguinis infection. Neospora caninum infection in an adult sheep and her twin fetuses. Plasma cell tumor. After a short introduction, the bibliographical data, the abstract of the author(s), and some additional information derived from the article are given. The article will be regularly updated adding overlooked as well as new first reports.